The nasal cavity represents an easily accessible and effective route of vaccination by which not only systemic, but also mucosal immunity, can be induced. Nasal vaccination is easy to administer and is suitable for mass immunization. New and existing vaccines can potentially be delivered via this route. The overall goal is to develop a simple and broad nasal vaccine delivery platform that prolongs the antigen residence time, enhances immune response, provides an easy formulation process, and is suitable for many different types of antigens. This platform, trademarked as GelVac, is based on a unique high molecular weight acidic polysaccharide (GelSite TM polymer). The GelSite polymer is capable of gelling in-situ, or changing from liquid to a gel upon contact with nasal fluids, thereby providing a controlled release of the antigen. Preliminary studies have provided an initial proof-of-concept for the GelVac platform by demonstrating in situ gelling in the nasal cavity, prolonged nasal residence, and increased serum IgG and lung IgA immune response against a model antigen (DT-CRM, diphtheria toxin mutant CRM) following intranasal delivery. This proposal seeks to establish the GelVac platform by determining its basic functional properties in relation to its effect on immune response and protection. Specifically, this study will examine and determine 1) the nasal residence times of the gel and antigen, 2) factors affecting antigen release, 3) formulation parameters for different antigens, and 4) immune response and protection following intranasal delivery in the presence or absence of an adjuvant. The feasibility of this platform as a broad nasal vaccine delivery vehicle will be demonstrated using different types of antigens including proteins (DT-CRM and tetanus toxoid), polysaccharide-protein conjugate (Haemophilus influenzae b polysaccharide-protein conjugate), and viral particles (rotavirus and influenza virus). These studies will form the basis for phase II development of this platform targeting demonstration of safety and efficacy against selected pathogens that have significant unmet medical and biodefense needs in humans.